9 resultados para BIOLOGICAL RELEVANCE

em Deakin Research Online - Australia


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Birds are a particularly good group with which to examine the importance of maternal effects, as parental contributions can be relatively easily quantified compared with other groups. There have undoubtedly been more studies on maternal effects in the Zebra Finch than any other single bird species. Studies of this species have examined the importance of maternal effects mediated through sex allocation, size, nutrients and hormones of of eggs, incubation behaviour and provisioning levels. A synthesis of all of this work illustrates some contrasting results (e.g. many high-profile results have failed to be replicated), some very common patterns (e.g. investment shifts through the laying sequence), and potentially interesting and complex interactions between traits (e.g. between sex of offspring and hormonal profiles of eggs). This extensive collection of work on the Zebra Finch provides useful general insight into the patterns of maternal investment in birds and the effects on offspring phenotype. However, we caution that the literature is probably littered with studies that have overemphasised the importance of some maternal effects and recent studies have highlighted analytical and logical flaws that have probably led to misplaced confidence in some of the findings reported to date. Finally, it is worth considering that the bulk of the literature is based on studies of captive domesticated birds and ecological and physiological data from individuals in the wild is currently lacking. The biological relevance of maternal effects documented in this model species is therefore unclear.

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Insulin resistance is a heterogeneous disorder caused by a range of genetic and environmental factors, and we hypothesize that its aetiology varies considerably between individuals. This heterogeneity provides significant challenges to the development of effective therapeutic regimes for long-term management of type 2 diabetes. We describe a novel strategy, using large-scale gene expression profiling, to develop a Gene Expression Signature (GES) that reflects the overall state of insulin resistance in cells and patients. The GES was developed from 3T3-L1 adipocytes that were made ‘insulin resistant’ by treatment with tumour necrosis factor-alpha (TNFα) and then reversed with aspirin and troglitazone (‘re-sensitized’). The GES consisted of five genes whose expression levels best discriminated between the insulin resistant and insulin re-sensitized states. We then used this GES to screen a compound library for agents that affected the GES genes in 3T3- L1 adipocytes in a way that most closely resembled the changes seen when insulin resistance was successfully reversed using aspirin and troglitazone. This screen identified both known and new insulin sensitizing compounds including non-steroidal anti inflammatory agents, β-adrenergic antagonists, beta-lactams and sodium channel blockers. We tested the biological relevance of this GES in participants in the San Antonio Family Heart Study (n = 1,240) and showed that patients with the lowest GES scores were more insulin resistant (according to HOMA_IR and fasting plasma insulin levels, P < 0.001). These findings show that GES technology can be used for both the discovery of insulin sensitizing compounds and the characterization of patients into subtypes of insulin resistance according to GES scores, opening the possibility of developing a personalized medicine approach to type 2 diabetes.

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Recent developments in ecological statistics have reached behavioral ecology, and an increasing number of studies now apply analytical tools that incorporate alternatives to the conventional null hypothesis testing based on significance levels. However, these approaches continue to receive mixed support in our field. Because our statistical choices can influence research design and the interpretation of data, there is a compelling case for reaching consensus on statistical philosophy and practice. Here, we provide a brief overview of the recently proposed approaches and open an online forum for future discussion (https://bestat.ecoinformatics.org/). From the perspective of practicing behavioral ecologists relying on either correlative or experimental data, we review the most relevant features of information theoretic approaches, Bayesian inference, and effect size statistics. We also discuss concerns about data quality, missing data, and repeatability. We emphasize the necessity of moving away from a heavy reliance on statistical significance while focusing attention on biological relevance and effect sizes, with the recognition that uncertainty is an inherent feature of biological data. Furthermore, we point to the importance of integrating previous knowledge in the current analysis, for which novel approaches offer a variety of tools. We note, however, that the drawbacks and benefits of these approaches have yet to be carefully examined in association with behavioral data. Therefore, we encourage a philosophical change in the interpretation of statistical outcomes, whereas we still retain a pluralistic perspective for making objective statistical choices given the uncertainties around different approaches in behavioral ecology. We provide recommendations on how these concepts could be made apparent in the presentation of statistical outputs in scientific papers.

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Abstracts: Lipid rafts are defined as specialized, dynamic microdomains that can be found in plasma membrane, and they are enriched with cholesterol and sphingolipids. Since lipid rafts’ first debut in the mid 1990’s, their existence, function and biological relevance have been a subject of intense scrutiny within the scientific community. Throughout this debate, we have learned a great deal regarding how cargos (both pathogens and cellular factors) are transported into and out of the cell through raft-dependent or raft-independent pathways. It is now apparent that a number of toxins, bacterial-, and viral-pathogens are able to exploit cholesterol and/or lipid rafts to gain a foot hold in their target hosts. The objective of this review is to describe our current appreciation on how selected pathogens utilise cholesterol and/or lipid rafts to support their propagation and to speculate on how some of these observations can be explored for the development of novel strategies that target plasma membrane lipids to control the spread of these viral- and bacterial-pathogens.

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The ability to spatiotemporally identify the formation of specific anionic species, or track changes in their concentration inside living systems, is of critical importance in deciphering their exact biological roles and effects. The development of probes (also called bioimaging agents and intracellular sensors) to achieve this goal has become a rapidly growing branch of supramolecular chemistry. In this critical review the challenges specific to the task are identified and for a select range of small anions of environmental and biological relevance (fluoride, chloride, iodide, cyanide, pyrophosphate, bicarbonate, hydrosulphide, peroxynitrite, hypochlorite and hypobromite) a comprehensive overview of the currently available in vitro and in vivo probes is provided.